One of the primary functions of the vascular system is to supply functioning tissues with nutrients and to remove metabolic by-products from the tissue. This function is achieved by maintaining adequate blood flow to and from the tissue. Changes in tissue blood flow occur by changing the tone of the blood vessels feeding the tissue, the arteries and arterioles. While changes in blood flow are mediated through changes in arteriolar tone, tissue exchange occurs at sites beyond the arteries and arterioles. Therefore there must be some mechanism(s) by which tissue needs at the level of the capillaries (exchange vessels) and venules (which conduct blood from the tissue) are transduced to the vessels which supply the tissue. Several studies have shown that application of vasoactive agents to venular segments results in an arteriolar response (dilation or constriction dependent on the agent). This occurs in both arterioles which are paired with venules as well as in arterioles which come in contact with venular segments. This proposal will determine a role for venular-arteriolar (V- A) communication in the regulation of arteriolar tone. In particular, we test the hypotheses that V-A communication is mediated by 1) venular endothelium derived nitric oxide and, 2) increased venular concentrations of tissue metabolites. The data obtained from these studies will provide important information regarding control of tissue perfusion. Further, this work represents new information about how vascular arrangement and environment can participate in the global control of tissue blood flow.